THEGAYUK

Author: Colvis Palmer

  • COMMENT | Why Is Finding A HIV Cure So Difficult?

    Doctor Clovis Palmer discusses why finding a cure for HIV is so difficult.

    HIV hijacks the immune system
    HIV hijacks the immune system’s white blood cells and forces them to make new copies of the virus. Treatment with antiretroviral drugs is remarkably effective at suppressing the virus, and most people who take HIV antiretroviral treatment are able to reduce the amount of HIV circulating in their bloodstream to undetectable levels. However, this treatment is unable to eliminate a tiny but tenacious type of infected white blood cells that contain a copy of the virus’s genetic material. These cells can remain in the body for a very long period, and they allow the virus to re-emerge and cause new rounds of infection if antiretroviral therapy (or ART) is ever interrupted. This is why daily, life-long HIV treatment is essential.

    Functional versus sterilising cure
    Given the challenges of delivering complex, expensive and potentially toxic HIV antiretroviral treatments on a global scale, there is intense interest in developing short-term, well-tolerated treatments that allow individuals to interrupt therapy indefinitely without the virus re-appearing in their blood. This so-called “functional cure” or “remission” will most likely be due to incomplete eradication of all the ‘sleeping HIV’, otherwise known as the HIV reservoir in the body. A sterilising cure on the other hand, which means complete eradication of HIV, will be a more challenging task, particularly if we rely solely on prolonged antiretroviral treatment to eliminate the reservoir. Recent interventions such as stem cell transplant, and very early initiation of antiretroviral therapy, suggest that considerable reductions in the reservoir size are possible but will not be sufficient for a complete cure.

    Major setback for an HIV cure as ‘cured’ infants relapse
    Any hopes that early HIV treatment initiation would be of any long-term benefit, at least in regards to treatment interruption, were given a major setback when reports earlier this year revealed HIV has returned in an infant previously pronounced ‘cured’. The infant was born with HIV infection in December 2009, and was given antiretroviral therapy (ART) within 12 hours of birth. Using the most sensitive laboratory test, HIV was undetectable in the child 3 years later.

    In view of this result, and in agreement with the child’s mother, the doctors stopped antiretroviral therapy. Encouragingly, a week later, HIV was undetectable, but remarkably, the virus reappeared a week later. This news followed an earlier report where HIV returned in yet another infant; the so-called Mississippi child who was born with HIV infection, and was believed to be cured after treatment administration soon after birth. These results dampen any hopes for an HIV cure that envisages exploiting early treatment and ART intensification as a cure strategy – at least using the current treatment modalities.

    “Shock” but no “Kill”
    More recently, another HIV cure approach delivered more disappointing results when a study using the so-called “shock and kill” approach failed to reduce the size of the HIV reservoir in patients. This approach depended on the ability of the virus itself or the patient’s immune system to kill infected cells when the ‘resting HIV’ is awakened. In this study, scientists used a drug called panobinostat, which has been shown to wake up HIV in the test tube. It was expected that this drug, when given in combination with standard antiretroviral treatment, would purge the reservoir. However, analysis of blood cells from patients revealed that this approach was ineffective. The drugs ‘woke up’ the virus but disappointingly; at the end of the study the size of the HIV reservoir remained unchanged.

    These HIV cases raise several important and puzzling questions. The disappointing study results may desensitise the public’s perception of an HIV cure. Are the media and researchers culpable for drumming up the hype that surrounds previous ‘HIV cure’ announcements? Scientists are aware of the limitations to reasonably access HIV in every cell in the body; unless we can analyse every HIV reservoir it will be difficult to convincingly declare someone as ‘cured’. Organs such as the brain, skin, gut, liver, spleen and testes are considered HIV sanctuaries. Given ethical and technical considerations, it will be virtually impossible to conduct appropriate HIV tests in every potential sanctuary. Even if more sensitive tests are developed, one major limitation will still remain: we cannot access where we truly need to measure the virus. So, should researchers be more cautious and perhaps describe these cases in the future as ‘temporary HIV remission’?

    The way forward
    In the December issue of The Lancet HIV, Professor Suzanne Crowe AM, from the Burnet Institute, and I recently highlighted several key issues that should be considered in the future for a more effective “shock and kill” approach. One of these issues is a greater understanding of how the drugs used in this cure strategy affect the immune cells. We know that they can ‘wake up’ the virus, but our understanding of the impact these drugs have on the immune cells where the virus hides is still limited. Scientists have now proposed a new way by which HIV remains indefinitely in the body. Rather than the virus replicating and re-infecting other immune cells, it is the cells that contain the sleeping virus that replicate, consistently re-fuelling the HIV reservoir. We proposed that starving these replicating cells of glucose, a major nutrient required by immune cells, is a potential strategy to decay the virus.

    by Doctor Clovis Palmer

    About the author
    Dr Clovis Palmer has authored several high impact scientific articles and reviews in HIV and obesity-related research, including The Lancet HIV, AIDS, Hepatology, and Gut. He is a reviewer for several international journals including Hepatology, AIDS, Journal of the International AIDS Society, Journal of Leucocyte Biology and Antioxidants and Redox Signalling. He is the chief section editor for HIV at Natural Immunity-Health, Australia (www.naturalimmunity.com.au).

     

    Opinions expressed in this article may not reflect those of THEGAYUK, its management or editorial teams. If you’d like to comment or write a comment, opinion or blog piece, please click here.

  • COMMENT | The Dangerous Relationship Between Obesity and HIV

    The Dangerous Relationship Between Obesity and HIV

    According to recent data from the SUN (Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy), which includes 494 patients, approximately 61% were either overweight or obese. Obesity was associated with insulin resistance, elevated cholesterol, increased inflammation and atherosclerosis.

    A reduction of dietary intake of 500 calories per day for 8 weeks resulted in a 6% decrease in body weight. What was remarkable in this study was the dramatic decline in systemic inflammation observed in the study participants. Indeed, two reputable markers of inflammation, tumour necrosis factor (TNF) and C-reactive protein, were reduced by almost 50% in only 8 weeks of calorie reduction.

    Inflammatory diseases such as diabetes, cardiovascular disease (CVD), kidney problems, osteoporosis, cogitative impairment and fragility, are becoming increasingly common in people living with HIV. As the prevalence of obesity and HIV-associated co-morbidities continues to rise, and concerns for the spiralling economic and social costs escalate, innovative management strategies beyond primary care are urgently needed. Many traditional lifestyle interventions can be implemented with the assistance of professionals, including:

    • Maintain a maximal viral suppression with antiretroviral therapy
    • Reduce or stop smoking
    • Lose at least 5-10% of body weight (if overweight)
    • Exercise
    • Consume more fruits and vegetables
    • Reduce alcohol intake

    One reason why people who are infected with HIV have high levels of inflammation is that HIV destroys the structure of the intestine (gut), causing bad bacteria to strive, and changes the dynamics of the gut microbiota.

    Toxins produced by bad bacteria cross the wall of the intestine and into the blood stream to instigate and fuel inflammation, and cause age-associated diseases. Similarly, alterations of the gut microbiota and mucosal barrier have been identified as a novel CVD risk factor and are associated with metabolic diseases such as obesity and type 2 diabetes.

    Incredibly, probiotic treatment using Bifidobacterium animalis ssp. lactis 420 has shown great promise in reducing body weight and liver inflammation in animal models.

    The increasing prevalence of obesity and type 2 diabetes demonstrates the difficulties of conventional treatments and interventions to curb these diseases. Efforts to identify new therapeutic strategies to modulate gut microbiota are now a high priority for public health and, to date, probiotics and/or prebiotics seem to be the most effective tools.

    Diet, especially high intake of fermentable fibres and plant polyphenols, appears to regulate microbial activities within the gut, supporting regulatory guidelines that encourage increased consumption of whole-plant foods (fruit, vegetables and whole-grain cereals) and providing the scientific rationale for the design of efficacious prebiotics.

    Polyphenol-rich cranberry extract has been proven to protect mice from diet-induced obesity and insulin resistance, although the effect might have been mediated by the regulation of intestinal inflammation. Recent human studies with carefully selected probiotic strains have shown that ingestion of viable micro-organisms with the ability to hydrolyse bile salts could lower blood cholesterol, a recognised risk factor in obesity-related CVD.

    1. Overton ET. Metabolic complications of HIV infection and its therapies. Top Antivir Med 2014,22:651-654.
    2. Palmer CS. Inflammation speeds up the aging process in people infected with HIV, 2014, http://www.naturalimmunity.com.au/hiv.html#B.
    3. Palmer CS, Crowe SM. How does monocyte metabolism impact inflammation and aging during chronic HIV infection? AIDS Res Hum Retroviruses 2014,30:335-336.
    4. Stenman LK, Waget A, Garret C, Klopp P, Burcelin R, Lahtinen S. Potential probiotic Bifidobacterium animalis ssp. lactis 420 prevents weight gain and glucose intolerance in diet-induced obese mice. Benef Microbes 2014,5:437-445.

    Dr Clovis Palmer is a graduate of the University of Sydney, Australia, and holds a PhD in plant biochemistry and molecular genetics. He conducted postdoctoral studies in immunology, liver disease and obesity at the University of New South Wales, Australia.

    Dr Palmer is a reviewer for several top ranked international journals including Hepatology, AIDS and Antioxidants and Redox Signalling. He is the chief scientific editor for Natural Immunity-Health, Australia (www.naturalimmunity.com.au).

     

    Opinions expressed in this article may not reflect those of THEGAYUK, its management or editorial teams. If you’d like to comment or write a comment, opinion or blog piece, please click here.

  • How to fight obesity naturally

    Natural remedies for fighting obesity

    CREDIT: ©-tish1-Depositphotos

    Anti-obesity drugs can have some hazardous side effects which make the use of natural supplements more attractive. Most drugs that fight obesity either do it by reducing fat absorption or by suppressing appetite through neuronal regulation. There are some fruit and herbal extracts that are found to possess components that can regulate body weight through similar mechanisms.

    Polyphenols inhibit pancreatic lipase
    Pancreatic lipase (PL) is crucial in regulating the digestion of fats into absorbable forms. Saponins, polyphenols, flavonoids and caffeine have been found to possess PL-inhibitory activity. These compounds are found naturally in different types of tea, oolong, green and black. They are also found in fruits like berries, apples, lemons and in grape seeds and several other herbs. A multitude of studies have sought to explore the anti-obesity effect of polyphenol-rich extracts in animal models and have found promising results.

    Hoodia and Garcina species suppress appetite
    Another way to reduce weight gain is to suppress appetite by regulating the respective control centres of the brain. The perception of fullness has been linked with the intake of some herbal extracts like, Hoodia gordonii and Hoodia pilifera, leafless plants common in South Africa. Cissus quadrangularis and Garcina cambogia possess natural hydrocitric acid which boosts the release of serotonin, a neurotransmitter that regulates appetite. Garcina exerted anti-obesity functions by reducing lipid accumulation in adipocytes in experiments on cell cultures.

    There are many supplements that contain extracts from Hoodia, Garcinia and Cissus plants and have proven to be effective in suppressing appetite and promoting weight loss. However, the exact mechanism by which this regulation is achieved by these extracts is not clear. Crude ethanol extract from Caralluma fimbriata, a type of cactus, and saponins from Korean red ginseng, have also been shown to have a suppressive effect on the hunger cycle.

    Fish oil
    Consumption of fish oil has also been linked to increased energy expenditure. Diet composed of eicosapentaenoic acid (EPA) and Dosahexaenoic acid (DHA), both components of fish oil, decreased body weight gain in mice. DHA caused 90% increase in lipolysis in different studies.

    Caffeine, rich in oolong tea
    The principal component of tea leaves, caffeine, has shown a reduction in weight gain through numerous mechanisms. Caffeine has lipolytic action and therefore increases lipid metabolism in the body. Increasing the energy expenditure of the body through non-shivering thermogenesis is also a way to regulate body weight. Caffeine and catechins found in tea have shown increased energy expenditure in multiple experiments.

    Ginseng
    Panax ginseng, a type of berry common in Korea, expresses moderate anti-obesity properties by suppressing appetite, increasing energy expenditure, and downregulating accumulation of triglycerides. The active components of ginseng that are used in supplements are ethanol extracts, ginsenosides and saponins.

    Resveratrol and quercetin
    Naturally occurring compounds like resveratrol, found in grapes and berries and quercetin, found in teas, apples and onions, are also associated with reduced accumulation of triglycerides. Resveratrol and quercetin inhibit adipogenesis and promote apoptosis in adipocytes and can therefore be used as an anti-obesity treatment.

    Other than the above mentioned compounds, extracts from cinnamon, garlic, capsicum, palm oil and green tea have also demonstrated anti-obesity properties in studies.

    Dr Clovis Palmer heads the immunometabolism group at the world renowned Burnet Institute of Medical Research in Melbourne, Australia. Dr Palmer is a reviewer for several top ranked international journals including Hepatology, AIDS and Antioxidants and Redox Signalling. He is the chief scientific editor for Natural Immunity-Health, Australia (www.naturalimmunity.com.au).

  • Is HIV medication making you suicidal?

    HIV drug increases risk of suicidal ideation.

    A recent study shows an association between Efavirenz (a common anti-HIV drug) and increased risk for suicidal ideation or attempted or completed suicide. The study conducted by Mollan KR et al., and published in Ann Intern Med. 2014 confirmed the neuropsychiatric effects of Efavirenz. With increased life expectancy of people living with HIV infection – and the opportunity to study the long term effects of drugs – the emergence of drug-induced co-morbidities is concerning.

    This underscores the need for the development of longer-acting drugs or treatment modalities that limit the constant (daily) use of antiretroviral therapy. Emerging data also beg the question as to the longer-term benefits of immediate treatment of a young individual with normal CD4 T cell count and low viral load.

    Indeed, early treatment reduces inflammation and impacts the size of the viral reservoir – yet the clinical benefits are questionable.

    One argument for early treatment is epidemiological-based: “to protect the community”. But we probably can dismiss this one because with fashionable PrEP picking up steam we might all be chewing PrEP candies in the near future.

    I think more needs to be done to delay the use of antiretroviral drugs wherever possible, and more reliable measures of inflammation are needed so that we are not only guiding treatment based on CD4 cell counts and viral load but also take into account the levels of inflammation a person has. After all, inflammation (which generally is associated with CD4 T cell count) has been shown to be the best predictor of HIV disease progression and mortality.

    Dr Clovis Palmer is a graduate of the University of Sydney, Australia, and holds a PhD in plant biochemistry and molecular genetics. He conducted postdoctoral studies in immunology, liver disease and obesity at the University of New South Wales, Australia.

    Dr Palmer is a reviewer for several top-ranked international journals including Hepatology, AIDS and Antioxidants and Redox Signalling. He is the chief scientific editor for Natural Immunity-Health, Australia (www.naturalimmunity.com.au).

     

    Opinions expressed in this article may not reflect those of THEGAYUK, its management or editorial teams. If you’d like to comment or write a comment, opinion or blog piece, please click here.

  • Theory: What causes the loss of CD4 T cells in people infected with HIV?

    A Theory for HIV infection: What causes the loss of CD4 T cells in people infected with HIV?

    HIV infection causes dysfunction and destruction of CD4 T cells that, without antiretroviral therapy (ART: a cocktail of drugs that interrupts the HIV life cycle), result in AIDS and eventual death within 7 to 10 years).
    Scientists believe that most CD4 T cells die, not because of direct infection by HIV of these cells, but through a process called inflammation, by which immune cells secrete toxic molecules to get rid of the virus.

    However, the logic behind how inflammation causes cell death has been a mystery for decades.

    But now, research conducted by scientists at the Burnet Institute in Melbourne, Australia, and published in the premiere HIV/AIDS Journal, AIDS in 2014, shows for the first time that HIV infection not only disturbs the functions of CD4 T cells but affects how these cells use energy (1). The team, led by chief investigator Dr Clovis Palmer, proposed a new model of how CD4 T cells are destroyed in people infected with HIV.

    In healthy persons, immune cells such as CD4 T cells take up low levels of glucose through a protein known as Glucose transporter 1 (Glut1). By a series of steps the glucose is broken down to produce pockets of energy called adenosine triphosphate (ATP) to maintain the general wellbeing of the cells

    The Burnet team showed that the Glucose transporter (Glut1) level is increased on CD4 T cells in people infected with HIV, and that this causes more glucose to enter the cells. This is a survival mechanism because the CD4 T cells need more energy to divide and manufacture antiviral and inflammatory molecules to fight the infection. This is what is called CD4 T cell activation or immune activation.
    In this activated state, instead of breaking down glucose to form energy pockets (ATP), glucose is broken down into a substance called lactic acid through a process called aerobic glycolysis. Glycolysis is only moderately efficient in energy production and, as a result, the CD4 T cells die of exhaustion. The researchers called this process ‘metabolic exhaustion’

    Dr Palmer believes that this finding could lead to new drugs that delay the start of anti-retroviral therapy and will strengthen the immune systems of HIV-positive people.

    Healthy adults have between 600 to 1,200 CD4 T cells in their blood but up to 30 percent of HIV infected adults have a CD4 cell count consistently less than 350, well below the normal range despite being on ART and having undetectable viral load. The team showed that glycolysis remains elevated in CD4 T cells from these persons and that this could explain why they are unable to reconstitute their normal CD4 T cell levels. These low levels of CD4 T cells put HIV-positive people on ART at higher risk of cardiovascular disease, liver disease, kidney failure and other life-threatening diseases.

    The results from this study suggest that CD4 T cells in HIV infected people cannot replenish themselves because they exhaust their energy reserves through their high metabolic activity. What’s exciting about this is a very real scenario where, by returning metabolic activity to normal, these cells could be re-energised to fight the infection by themselves.

    Dr Clovis Palmer heads the immunometabolism group at the world renowned Burnet Institute of Medical Research in Melbourne, Australia. Dr Palmer is a reviewer for several top-ranked international journals including Hepatology, AIDS and Antioxidants and Redox Signalling. He is the chief scientific editor for Natural Immunity-Health, Australia (www.naturalimmunity.com.au).

    by Doctor Clovis Palmer

     

    Opinions expressed in this article may not reflect those of THEGAYUK, its management or editorial teams. If you’d like to comment or write a comment, opinion or blog piece, please click here.

  • Commentary | Turning Back the Clock on HIV

    Growing Old with HIV

    Life expectancy has increased remarkably in HIV+ people. This is due to the improved efficacy of antiretroviral drugs. However, according to a recently published article, “Inflammatory Co-morbidities in HIV+ Individuals: Learning Lessons from Healthy Ageing” by lead authors Dr Anna Hearps and Professor Suzanne Crowe at the Burnet Institute in Australia, this comes with a price [1].

    “Increased life expectancy in HIV+ individuals has uncovered an increased risk of acquiring age-related conditions such as cardiovascular diseases, neurocognitive decline, osteoporosis and frailty.”

    The authors linked these conditions to inflammation that causes premature ageing of the immune system. The immune system of young HIV+ people resembles that of uninfected elderly people.

    Where Does Inflammation Come From?
    Damage to the lining of the intestine during HIV infection is thought to cause leaking of bacterial products into the blood stream and this contributes to inflammation. Chronic Inflammation is a feature of ageing and is recognised as the driving force behind many age-related diseases. HIV infected individuals have high levels of inflammation even in those receiving anti-retroviral therapy (ART) and who have undetectable viral load. In fact, as shown in the Data collection on Adverse events of Anti-HIV Drugs (DAD) study [2], a non-smoking HIV+ person on ART and a long-term smoker face the same health risk of developing heart disease.

    Therapies
    Preventing or treating inflammatory diseases by reducing inflammation seems an obvious approach. Unfortunately, as there is no “magic bullet” pill, healthy lifestyle choices remain the most effective way to control inflammation. Low-dose aspirin (baby aspirin) is commonly used as a preventative strategy for heart attack in the general population. The medical world holds its breath for results from a large Australian study (ASPREE) that has been evaluating the efficacy of low-dose aspirin treatment over a 5 year period, in preventing age-related conditions in 19,000 elderly individuals. Other drugs such as statins and hydroxychloroquine have been evaluated, but adding yet another drug to the already complex HIV regimen is not an inviting prospect for those already on a cocktail of pills. Furthermore, the long-term effects of these drugs are unknown. Some evidence suggests that probiotics and a Mediterranean diet could be beneficial although more studies are warranted.

    The Future
    The majority of studies conducted examined a limited number of biomarkers that consistently show a strong relationship with several age-related co-morbidities and therefore may have diagnostic potential. The main challenge that remains is to understand how these association studies can pinpoint the mechanisms involved in these clinical manifestations to engender novel therapeutics to delay the onset of pre-mature ageing in the HIV+ population. Most importantly, these novel strategies should be long lasting, perhaps once per week or once per month, to limit additional pill burden.

    References
    1. Hearps A.C, Martin G.E, Rajasuriar R, Crowe S.M: Inflammatory Co-morbidities in HIV+ Individuals: Learning Lessons from Healthy Ageing. Current HIV/AIDS Reports (2014).
    2. Friis-Moller N, Thiebaut R, Reiss P, Weber R, Monforte A.D, De Wit S, El-Sadr W, Fontas E, Worm S, Kirk O, et al: Predicting the risk of cardiovascular disease in HIV-infected patients: the data collection on adverse effects of anti-HIV drugs study. European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology (2010), 17:491-501.

    About the author
    Dr Clovis Palmer heads the Immunometabolism research team at the Burnet Institute in Melbourne, Australia. He recently identified a new subset of immune cells and is the first to show that HIV affects the way CD4 T cells use energy – a discovery that could revolutionize the prognosis and treatment of people infected with HIV. He frequently speaks at The International AIDS Society/AIDS conferences and is a guest editor and reviewer for several top ranked scientific journals. He is the Founder of Natural Immunity-Health, a scientifically driven organization that promotes a healthy lifestyle in order to combat inflammatory conditions such as HIV and obesity. Dr Palmer’s work has also been featured in The Australian Sydney Morning Herald and The AGE: http://www.smh.com.au/digital-life/digital-life-news/ideas-that-could-change-your-life-20130312-2fxo6.html, and the Star Observer: http://www.starobserver.com.au/news/study-finds-new-route-against-hiv/90705.

     

    Opinions expressed in this article may not reflect those of THEGAYUK, its management or editorial teams. If you’d like to comment or write a comment, opinion or blog piece, please click here.